This research is aimed at elucidating the structural and metabolic relationships of the multiple forms of ferritin found within single tissues. These structural studies will be complemented by metabolic studies of the protein shells and iron cores in response to administration of different types and amounts of iron. The major isoferritins from different regions of the spectrum will be characterized by their pI, subunit composition, and iron content. Detailed structural studies will be made of the different types of ferritin subunits by analyses of amino acid composition, N and C terminal amino acids, and peptide patterns given after cleavage with cyanogen bromide, 2-nitro-5-thiocyanobenzoic acid and trypsin. The immunological relationships of these subunits will also be investigated. Attempts will be made to analyze packing arrangements of the subunits in the hybrid molecules and to determine whether this packing affects the ability of the shell to take up or release iron. These structural studies will be performed on both human and horse ferritins. In related studies, we will examine the distribution and metabolism of isoferritins in rat tissues such as liver, spleen, heart, and kidney in response to different forms of iron treatment and withdrawal. The relative rates of synthesis and turnover of the protein shells and of their iron cores will be investigated by tracer studies. These findings will be related to other parameters of iron metabolism such as intracellular distribution between ferritin, hemosiderin and the chelatable iron pool.